We propose to study the potential involvement of certain "oncodevelopmental" genes in cellular processes related to development and leukemogenesis. The genes concerned are endogenous retrovirus-related nucleotide sequences and the model system proposed is the outbred domestic cat harboring genetic sequences of two well-characterized, unrelated retroviruses. Differential expression in these endogenous genes in developing feline tissues and their widespread expression in feline leukemia-lymphoma are not generally associated with full expression and release of infectious virus. Developing tissues like placenta and fetal thymus will be investigated for the nature and processing of endogenous viral transcripts, for the relationship of the steady-state occurrence of the transcripts to translational products and for identification of cell types responsible for the expression. Normal and malignant feline lymphoid cells will be examined for the relationship between patterns of expression of these sequences as RNA, as cell surface proteins or polyproteins and the phenotypic alterations. Necleotide sequence homology between endogenous and exogenous feline leukemia virus genomes will be examined and the results will be used to ascertain the degree of heterogeneity that might exist in the RNA sequences. The messenger RNA activity of the endogenous leukemia virus-related sequences will be tested for in vitro translation and the polypeptide products, if formed, will be tested for immunologic and peptide relationship to viral proteins and to virus induced tumor antigens. The biochemical methodology will include techniques of molecular hybridization, oligonucleotide fingerprinting, immunoprecipitation, cell surface radioiodination, two-dimensional tryptic peptide analysis, and other related technologies. Cell types responsive for specific endogenous retroviral expression will be identified by immunohistological procedures. The results will be useful in defining certain oncodevelopmental genes and their phenotypic expression.